CDK4 and neoplasm: The results of subsequent RNA-Seq and kinome analyses have continued to underscore reliance on the phosphatidyl-inositol-3-kinase/mammalian target of rapamycin (PI3K-mTOR) signaling axis [194] in CDK4/6 inhibitor-resistant cells, whereby mTORC1/2 inhibition in palbociclib-resistant cells reduces tumor growth [195, 196] and reactivates the CDK4/6-RB signaling node with commensurate changes in E2F-mediated transcription [195], without inducing a senescence-like phenotype.